A Multiple Dose Study of PF-04950615 (RN316) in Subjects on High Doses of Statins

Hypercholesterolemia Clinical Trial

Official title:

A Phase 2, Double-blind, Placebo-controlled, Randomized Study To Assess The Efficacy, Safety And Tolerability Of Pf-04950615 Following Multiple Intravenous Doses In Hypercholesterolemic Subjects On High Doses Of Atorvastatin, Rosuvastatin Or Simvastatin.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01342211
• Other study ID #: B1481005
• Status: Completed
• Phase: Phase 2
• First received: April 25, 2011
• Last updated: September 11, 2017
• Start date: July 2011
• Est. completion date: June 2012

Study information

• Verified date: September 2017
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will investigate the effect of PF-04950615, a new investigational lipid lowering agent, on LDL-C and other lipids.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 93
• Est. completion date: June 2012
• Est. primary completion date: February 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• On a stable daily dose of atorvastatin, rosuvastatin or simvastatin.

• Lipids meet the following criteria at screening and prior to dosing: Fasting LDL-C greater than 100 mg/dL and fasting TG less than 400 mg/dL

Exclusion Criteria:

• History of a cardiovascular or cerebrovascular event or procedure during the past year.

• Poorly controlled type 1 or type 2 diabetes mellitus.

• Poorly controlled hypertension.

Related Conditions & MeSH terms

• Dyslipidemia
• Dyslipidemias
• Hypercholesterolemia

Intervention

Biological:
• Placebo
Intravenous placebo monthly during treatment phase.

Drug:
• Statin
Single daily dose of atorvastatin (40 or 80 mg), rosuvastatin (20 or 40 mg) or simvastatin (40 or 80 mg) from Day 1 to Day 141/ET.

Biological:
• PF-04950615 (RN316)
Intravenous 10mg/mL based on weight monthly during treatment phase.

Drug:
• Statin
Single daily dose of atorvastatin (40 or 80 mg), rosuvastatin (20 or 40 mg) or simvastatin (40 or 80 mg) from Day 1 to Day 141/ET.

Biological:
• PF-04950615 (RN316)
Intravenous 10mg/mL based on weight monthly during treatment phase.

Drug:
• Statin
Single daily dose of atorvastatin (40 or 80 mg), rosuvastatin (20 or 40 mg) or simvastatin (40 or 80 mg) from Day 1 to Day 141/ET.

Biological:
• PF-04950615 (RN316)
Intravenous 10mg/mL based on weight monthly during treatment phase.

Drug:
• Satin
Single daily dose of atorvastatin (40 or 80 mg), rosuvastatin (20 or 40 mg) or simvastatin (40 or 80 mg) from Day 1 to Day 141/ET.

Biological:
• PF-04950615 (RN316)
Intravenous 10mg/mL based on weight monthly during treatment phase.

Drug:
• Statin
Single daily dose of atorvastatin (40 or 80 mg), rosuvastatin (20 or 40 mg) or simvastatin (40 or 80 mg) from Day 1 to Day 141/ET.

Locations

Country	Name	City	State
Canada	Q & T Research Chicoutimi	Chicoutimi	Quebec
Canada	The Medical Arts Health Research Group	Kelowna	British Columbia
Canada	Centre de Recherche Clinique de Laval	Laval	Quebec
Canada	Diex Research Montreal Inc.	Montreal	Quebec
Canada	Clinique des Maladies Lipidiques de Quebec Inc.	Quebec
Canada	Diex Research Sherbrooke Inc.	Sherbrooke	Quebec
United States	New Mexico Clinical Research & Osteoporosis Center, Incorporated	Albuquerque	New Mexico
United States	Maine Research Associates	Auburn	Maine
United States	Innovative Research of West Florida, Inc.	Clearwater	Florida
United States	Avail Clinical Research, LLC	DeLand	Florida
United States	In Vivo Clinical Research, Inc.	Doral	Florida
United States	Altoona Center for Clinical Research	Duncansville	Pennsylvania
United States	Texas Center for Drug Development, Inc.	Houston	Texas
United States	Jacksonville Center for Clinical Research	Jacksonville	Florida
United States	Saint Luke's Hospital	Kansas City	Missouri
United States	Saint Luke's Lipid and Diabetes Research Center	Kansas City	Missouri
United States	The Center for Pharmaceutical Research, P.C.	Kansas City	Missouri
United States	New Orleans Center for Clinical Research	Knoxville	Tennessee
United States	Volunteer Research Group	Knoxville	Tennessee
United States	L-MARC Research Center	Louisville	Kentucky
United States	Commonwealth Biomedical Research, LLC	Madisonville	Kentucky
United States	Kendall South Medical Center	Miami	Florida
United States	National Clinical Research - Norfolk, Inc.	Norfolk	Virginia
United States	Infinity Medical Research	North Dartmouth	Massachusetts
United States	Lynn Health Science Institute	Oklahoma City	Oklahoma
United States	Oklahoma Cardiovascular Research Group (OCRG)	Oklahoma City	Oklahoma
United States	Oklahoma Heart Hospital	Oklahoma City	Oklahoma
United States	Oklahoma Heart Hospital Physicians	Oklahoma City	Oklahoma
United States	Vince and Associates Clinical Research	Overland Park	Kansas
United States	Perelman Center for Advanced Medicine	Philadelphia	Pennsylvania
United States	Translational Research Center	Philadelphia	Pennsylvania
United States	North Carolina Clinical Research	Raleigh	North Carolina
United States	National Clinical Research - Richmond, Inc.	Richmond	Virginia
United States	Medex Healthcare Research, Inc.	Saint Louis	Missouri
United States	PMG Research of Salisbury	Salisbury	North Carolina
United States	Clinical Trials of Texas, Inc.	San Antonio	Texas
United States	Paragon Research Center, LLC	San Antonio	Texas
United States	San Antonio Preventive & Diagnostic Medicine, PA	San Antonio	Texas
United States	Spartanburg Medical Research	Spartanburg	South Carolina
United States	Orange County Research Center	Tustin	California
United States	Diablo Clinical Research, Inc.	Walnut Creek	California
United States	Heartland Research Associates, LLC	Wichita	Kansas
United States	North Georgia Clinical Research	Woodstock	Georgia
United States	North Georgia Internal Medicine	Woodstock	Georgia

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change From Baseline in Lipoprotein (a) (Lp[a]) at Day 29, 57, 71, 85, 99, 127 and 141	Baseline value was calculated as the average of Day 7 and Day 1 measurements collected prior to study drug administration.	Baseline, Day 29, 57, 71, 85, 99, 127, 141
Other	Percent Change From Baseline in Lipoprotein (a) (Lp[a]) at Day 29, 57, 71, 85, 99, 127 and 141	Baseline value was calculated as the average of Day 7 and Day 1 measurements collected prior to study drug administration.	Baseline, Day 29, 57, 71, 85, 99, 127, 141
Primary	Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Day 85	Baseline value was calculated as the average of Day 7 and Day 1 measurements collected prior to study drug administration.	Baseline, Day 85
Secondary	Percentage of Participants Achieving Low-density Lipoprotein Cholesterol (LDL-C) Less Than (<) 70 and <100 Milligram Per Deciliter (mg/dL)		Day 29, 57, 85
Secondary	Percentage of Participants Achieving at Least 30 Percent Decrease in Low-density Lipoprotein Cholesterol (LDL-C)		Day 29, 57, 85
Secondary	Change From Baseline in Lipid Parameters at Day 29, 57 and 85	Lipid parameters included: high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), non-high-density lipoprotein-cholesterol (non-HDL-C), triglyceride (TG), apolipoprotein B (ApoB) and apolipoprotein A1 (ApoA1). Baseline value was calculated as the average of Day 7 and Day 1 measurements collected prior to study drug administration.	Baseline, Day 29, 57, 85
Secondary	Percent Change From Baseline in Lipid Parameters at Day 29, 57 and 85	Lipid parameters included: high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), non-high-density lipoprotein-cholesterol (non-HDL-C), triglyceride (TG), apolipoprotein B (ApoB) and apolipoprotein A1 (ApoA1). Baseline value was calculated as the average of Day 7 and Day 1 measurements collected prior to study drug administration.	Baseline, Day 29, 57, 85
Secondary	Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAEs are events between first dose of study drug and up to Day 141 that were absent before treatment or that worsened relative to pretreatment state. Treatment related: a TEAE deemed related to the study drug by the investigator. TEAEs included SAEs (TESAEs) as well as non-serious AEs which occurred during the study. The participants with TEAEs, SAEs and treatment-related TEAEs were reported.	Day 1 up to Day 141
Secondary	Number of Treatment-Emergent Adverse Events (TEAEs) by Severity	An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. Investigator assessed TEAEs as mild (did not interfere with participant's usual function), moderate (interfered to some extent with participant's usual function) or severe (interfered significantly with participant's usual function). TEAEs are events between first dose of study drug and up to Day 141 that were absent before treatment or that worsened relative to pretreatment state.	Day 1 up to Day 141
Secondary	Number of Participants With Clinically Relevant Laboratory Abnormalities	Hematology (hemoglobin[hgb],hematocrit,red blood cell[RBC]<0.8*lower limit of normal[LLN],mean cell[MC] volume,MC hgb,MC hg concentration <0.9*LLN, greater than[>] 1.1*upper limit of normal[ULN], platelet <0.5*LLN,>1.75*ULN, white blood cell[WBC]<0.6*LLN,>1.5*ULN,neutrophil,lymphocyte <0.8*LLN,>1.2*ULN,eosinophil,basophil,monocyte >1.2*ULN);chemistry(total, direct, indirect bilirubin[BR]>1.5*ULN,aspartate aminotransferase[AT],alanine AT,alkaline phosphatase,gamma-glutyl transferase>3.0*ULN,protein,lactate dehydrogenase <0.8*LLN,>1.2*ULN,creatinine,blood urea nitrogen>1.3*ULN,uric acid >1.2*ULN,potassium,chloride,calcium,bicarbonate<0.9*LLN,>1.1*ULN, sodium<0.95*LLN,>1.05*ULN,glucose[GL]<0.6*LLN,>1.5*ULN,amylase,lipase >1.5*ULN,creatinine kinase>2.0*ULN);urinalysis(pH <4.5,>8,specific gravity<1.003 , >1.030, GL,ketone,protein,hgb,BR,nitrite,leukocyte greater than or equal to [>=]1, RBC, WBC >=20);coagulation(prothrombin[PT],PT international ratio,partial thromboplastin time>1.1*ULN).	Day 1 up to Day 141
Secondary	Number of Participants With Clinically Significant Changes in Vital Signs and Electrocardiogram (ECG) Parameters	Criteria for clinical significant vital signs: maximum increase or decrease from baseline in supine systolic blood pressure (BP) greater than or equal to (>=) 30 millimeter of mercury (mmHg), maximum increase or decrease from baseline in supine diastolic BP of >=20 mmHg. Criteria for clinically significant ECG parameters: maximum increase of >=25 percent (%) for baseline value of >200 millisecond (msec) and maximum increase of >=50% for baseline value of less than or equal to (<=) 200 msec for PR and QRS interval; maximum increase from baseline of >30 to <=60 msec and maximum increase from baseline of >60 msec for QT interval corrected using the Fridericia's formula (QTCF).	Day 1 up to Day 141
Secondary	Number of Participants With Anti-drug Antibody (ADA)	Human serum ADA samples of participants who received PF-04950615 (RN316) were analyzed for the presence of anti-PF-04950615 (RN316) antibodies by using the semi quantitative enzyme-linked immunosorbent assay (ELISA). Results with titer value >=4.32 nanogram per milliliter of anti-PF-04950615 antibodies were counted as positive. Number of participants with presence of anti-PF-04950615 antibodies were reported in this outcome measure.	Day 1 up to Day 141

External Links

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